{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:08:48Z","timestamp":1788768528055,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This prospective exploratory phase 2 study employed a three\u2010cohort, two\u2010phase design to evaluate the potential of anlotinib as a substitute for cisplatin in gemcitabine\u2013penpulimab combinations for metastatic nasopharyngeal carcinoma (NPC) patients who were previously treated with cisplatin\u2010based chemoradiotherapy. Patients enrolled in the study were randomized in a 1:1:1 ratio during the lead\u2010in phase to one of three treatment arms: gemcitabine, cisplatin, penpulimab, and anlotinib (GP\u2010PA,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098); gemcitabine, cisplatin, and penpulimab (GP\u2010P,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096); or gemcitabine, penpulimab, and anlotinib (GAP,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096). The expansion phase enriched the optimal cohort, with stratification based on PD\u2010L1 expression. The primary endpoints were safety and objective response rate (ORR), while the secondary endpoints included duration of response, disease control\u00a0rate (DCR), progression\u2010free survival (PFS), and overall survival (OS). In the lead\u2010in phase, grade \u2265\u20093 treatment\u2010emergent\u00a0adverse events (TEAEs) occurred in 87.5% (GP\u2010PA), 100% (GP\u2010P), and 66.7% (GAP) patients, predominantly hematologic toxicities. ORR\/DCR were 62.5%\/87.5% (GP\u2010PA), 83.3%\/100% (GP\u2010P), and 100%\/100% (GAP). At median 20.2\u2010month follow\u2010up, median PFS\/OS were 4.1\/18.4\u2009months for GP\u2010PA and not reached for GP\u2010P\/GAP. In the expansion phase, a total of 14 patients\u00a0received GAP, with an ORR of 93.3% and grade \u2265\u20093 TEAEs in 71.4% of patients. At data cut\u2010off point, the median PFS had not been reached, and the 12\u2010month PFS and OS rates were 53.8% and 78.6%, respectively. The GAP regimen demonstrated a favorable safety and efficacy profile, compared to the GP\u2010PA and GP\u2010P regimens in patients with metastatic NPC. These findings suggest that substituting cisplatin with anlotinib may offer a viable therapeutic strategy for this patient population.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70542","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T07:08:28Z","timestamp":1778137708000},"page":"2231-2243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Penpulimab and Gemcitabine With or Without Anlotinib in Metastatic Nasopharyngeal Carcinoma: A Randomized, Open\u2010Label, Multicenter Phase 2 Study"],"prefix":"10.1002","volume":"159","author":[{"given":"Shuang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Head and Neck Radiotherapy Zhejiang Cancer Hospital  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Qian","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Hunan 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